Clinicopathological Correlates of Hormone Expression-Based Subtypes of Non-Functioning Duodenal/Ampullary Neuroendocrine Tumors: A Multicenter Study of 151 Cases

Duodenal neuroendocrine tumors (Duo-NETs) may arise in the ampullary and non-ampullary duodenum. Non-functioning Duo-NETs (NF-Duo-NETs), which account for most cases, may express various hormones. Previous studies have suggested that hormone production might be associated with biological aggressiveness. Current treatment protocols are based on functionality, tumor size, and location, but small NF-Duo-NETs may also have metastatic potential. We aimed to investigate whether tumor cell subtyping, based on hormone expression, could provide further insights into NF-Duo-NET biological behavior. We analyzed the clinico-pathological correlates of hormone expression in a multicenter series of 151 NF-Duo-NETs, subdividing tumors into five subtypes: gastrin-producing G-cell NETs (Gas-NETs), somatostatin-producing D-cell NETs (Som-NETs), serotonin-producing enterochromaffin-cell NETs (Ser-NETs), plurihormonal NETs, and gastrin-, somatostatin-, and serotonin-negative NETs (GSSN-NETs). Som-NETs were the most frequent (31%), followed by plurihormonal NETs (26%), Gas-NETs (24%), GSSN-NETs (13%), and Ser-NETs (4%). Som-NETs and GSSN-NETs were more commonly located in the ampullary region and showed significantly larger size, more frequent lymphatic and/or vascular invasion, and higher pT, pN, and American Joint Committee on Cancer (AJCC-9th edition) stages compared to Gas-NETs, which were often (77%) diagnosed at AJCC stage I. Ampullary Som-NETs showed a more invasive and metastatic potential compared to non-ampullary Som-NETs, while, among plurihormonal NETs, the predominantly expressed hormone influenced tumor biological features, with gastrin-predominant NETs showing less invasive potential. At logistic regression, both tumor cell subtype and tumor size were independently associated with aggressiveness (pT3, pN1, or pM1 stage at diagnosis). Hormonal expression profiling may be clinically relevant in NF-Duo-NETs, independently of tumor size.

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Publication Details

Journal
Endocrine Pathology
Published
2025-05-10
DOI
https://doi.org/10.1007/s12022-025-09861-4
Citations
2
Primary Topic
Neuroendocrine Tumor Research Advances
Type
article
Field-Weighted Citation Impact
2.71

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article

Clinicopathological Correlates of Hormone Expression-Based Subtypes of Non-Functioning Duodenal/Ampullary Neuroendocrine Tumors: A Multicenter Study of 151 Cases

Luca Albarello, Aldo Scarpa, Federica Grillo, Silvia Uccella et al.
2 citations
Endocrine Pathology
Neuroendocrine Tumor Research Advances
2.71
article

Clinicopathological Correlates of Hormone Expression-Based Subtypes of Non-Functioning Duodenal/Ampullary Neuroendocrine Tumors: A Multicenter Study of 151 Cases

Luca Albarello, Aldo Scarpa, Federica Grillo, Silvia Uccella, Massimo Milione, Marco Paulli, Alessandro Vanoli, Guido Rindi, Paola Parente, Stefano La Rosa, Paola Mattiolo, Andrea A. Anderloni, Matteo Fassan, Frediano Inzani, Claudio Luchini, Massimo Falconi, Paola Spaggiari, Ombretta Luinetti, Catherine Klersy, Alessandro Zerbi, Nestor Piva, Marco Schiavo Lena, Antonio Di Sabatino, Anna Caterina Milanetto, Caterina Antoniacomi
article en
2 citations

Abstract

Duodenal neuroendocrine tumors (Duo-NETs) may arise in the ampullary and non-ampullary duodenum. Non-functioning Duo-NETs (NF-Duo-NETs), which account for most cases, may express various hormones. Previous studies have suggested that hormone production might be associated with biological aggressiveness. Current treatment protocols are based on functionality, tumor size, and location, but small NF-Duo-NETs may also have metastatic potential. We aimed to investigate whether tumor cell subtyping, based on hormone expression, could provide further insights into NF-Duo-NET biological behavior. We analyzed the clinico-pathological correlates of hormone expression in a multicenter series of 151 NF-Duo-NETs, subdividing tumors into five subtypes: gastrin-producing G-cell NETs (Gas-NETs), somatostatin-producing D-cell NETs (Som-NETs), serotonin-producing enterochromaffin-cell NETs (Ser-NETs), plurihormonal NETs, and gastrin-, somatostatin-, and serotonin-negative NETs (GSSN-NETs). Som-NETs were the most frequent (31%), followed by plurihormonal NETs (26%), Gas-NETs (24%), GSSN-NETs (13%), and Ser-NETs (4%). Som-NETs and GSSN-NETs were more commonly located in the ampullary region and showed significantly larger size, more frequent lymphatic and/or vascular invasion, and higher pT, pN, and American Joint Committee on Cancer (AJCC-9th edition) stages compared to Gas-NETs, which were often (77%) diagnosed at AJCC stage I. Ampullary Som-NETs showed a more invasive and metastatic potential compared to non-ampullary Som-NETs, while, among plurihormonal NETs, the predominantly expressed hormone influenced tumor biological features, with gastrin-predominant NETs showing less invasive potential. At logistic regression, both tumor cell subtype and tumor size were independently associated with aggressiveness (pT3, pN1, or pM1 stage at diagnosis). Hormonal expression profiling may be clinically relevant in NF-Duo-NETs, independently of tumor size.

Endocrine PathologyVol. 36(1)
Università Cattolica del Sacro Cuore (IT), University of Insubria (IT), University of Verona (IT), Humanitas University (IT), University of Padua (IT), Vita-Salute San Raffaele University (IT), University of Pavia (IT), Casa Sollievo della Sofferenza (IT), Agostino Gemelli University Polyclinic (IT), Saint Camillus International University of Health and Medical Sciences (IT), AULSS 2 Marca Trevigiana (IT), Ospedale Policlinico San Martino (IT), Policlinico San Matteo Fondazione (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), IRCCS Humanitas Research Hospital (IT), Pancreas Centre (Canada) (CA), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), Aziende Socio Sanitarie Territoriale dei Sette Laghi, University of Genoa (IT), Universidade Federal de São Paulo (BR)
Università degli Studi di Padova, Università degli Studi di Pavia
Good health and well-being
Openalex Percentile: Top 11%
Neuroendocrine Tumor Research Advances
2.71
DOIOpen Access PDFOpenAlex
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